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- Elhai, M, et al.
(författare)
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Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
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Tidskriftsartikel (refereegranskat)abstract
- To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
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- Mason, Richard J., et al.
(författare)
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Aquatic Insect Bioconstructions Modify Fine-Sediment Entrainment and Mobility
- 2022
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Ingår i: Journal of Geophysical Research - Earth Surface. - : American Geophysical Union (AGU). - 2169-9003 .- 2169-9011. ; 127:2
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Tidskriftsartikel (refereegranskat)abstract
- The importance of two-way interactions between animals and the physical hydraulic and sedimentological environment are increasingly recognized (e.g., zoogeomorphology). Caddisflies (Trichoptera) are a group of aquatic insects known for their bioconstructions, particularly cases built from fine sediment and silk. Caddisfly cases differ in size, shape and density from the incorporated sediment, and case construction may therefore affect the mobility of these sediments in rivers. However, although communities of caddisfly often use substantial quantities of sediment in case construction, the effect of these bioconstructions on sediment transport in rivers is unknown. We use a flume experiment to compare the bed shear stress required to transport (a) empty caddisfly cases and (b) individual sediment particles, following disaggregation from the case. The cases of three species were considered; two that construct different styles of tubular case (Potamophlax latipennis and Sericostoma personatum) and one that builds a domed case (Agapetus fuscipes). P. latipennis and S. personatum cases were easier to entrain than the sediment grains incorporated into them, whilst A. fuscipes cases were not. Despite their low mass, A. fuscipes cases required the most shear stress to transport them because their domed shape impeded rolling. These findings are important to understand how differences in case design between species, reflect different adaptation strategies to the turbulent hydraulic river habitat. Furthermore, the results suggest that un-attached tubular caddisfly cases may be preferentially transported over other particles on the river bed and thus, where caddisfly occur in high abundance, they may increase fluvial entrainment of sand.
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- Müller, Niels A., et al.
(författare)
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A single gene underlies the dynamic evolution of poplar sex determination.
- 2020
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Ingår i: Nature Plants. - : Springer Nature. - 2055-0278 .- 2055-026X. ; 6:6, s. 630-637
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Tidskriftsartikel (refereegranskat)abstract
- Although hundreds of plant lineages have independently evolved dioecy (that is, separation of the sexes), the underlying genetic basis remains largely elusive. Here we show that diverse poplar species carry partial duplicates of the ARABIDOPSIS RESPONSE REGULATOR 17 (ARR17) orthologue in the male-specific region of the Y chromosome. These duplicates give rise to small RNAs apparently causing male-specific DNA methylation and silencing of the ARR17 gene. CRISPR–Cas9-induced mutations demonstrate that ARR17 functions as a sex switch, triggering female development when on and male development when off. Despite repeated turnover events, including a transition from the XY system to a ZW system, the sex-specific regulation of ARR17 is conserved across the poplar genus and probably beyond. Our data reveal how a single-gene-based mechanism of dioecy can enable highly dynamic sex-linked regions and contribute to maintaining recombination and integrity of sex chromosomes.
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